The participation of the C3 protein in immune surveillance and immune response pathways has been well documented; however, information concerning the structural correlates of its biological activities has not been forthcoming. Activation of the complement system by the "classical" or "alternative" pathways results in a selective and controlled fragmentation of the C3 molecule. Interactions of C3 fragments with surface receptors of the PMN, B-cell and monocyte serve to modulate complementdependent granulocyte and lymphocyte functions. The elucidation of molecular features germane to these membrane directed complement functions will require (1) further characterization of the structures of the individual complement proteins involved, and (2) an evaluation of the physicochemcial basis for their binding properties. We intend to meet both of these requirements in our studies. The isolation of major activation fragments and subsequent chemical analysis will contribute to further structural delineation of the C3 molecule. Once the cleavage fragments of C3 with cell binding activities have been identified, specific peptide inhibition experiments should establish subregions of these ligands that constitute receptor binding sites. If such oligopeptides can be obtained, they may have specific application as inhibitors of in vivo C3:C3 receptor interations. Therefore, this approach has the potential of offering a new class of inhibitors to the processes involved in inflammatory reactions, especially in the class of autoimmune disorders.